The present invention relates to adhesion proteins and to methods of using them to promote the adhesion of keratinocytes to a substrate, e.g., to human dermis. In particular, KS-laminin, a new variant of laminin is disclosed.
Laminins are multimeric proteins involved in the adhesion between the human dermis and epidermis. Laminins generally includes three sub-units, a B1 chain, a B2 chain, an A chain. There are two known variants of B1 chain, the prototypic B1 exemplified by the B1e chain present in Englebreth-Holm-Swarm tumor laminin, (EHS-laminin) (Cooper et al., Eur. J. Bio. Chem. 119:189 (1981)); and B1s, exemplified by the B1 chain of S-laminin, a variant with 80% homology to EHS B1. The prototype B2 chain is the B2e chain of EHS-laminin. Laminin A chains includes the prototypic laminin A, referred to as Ae, found in EHS-laminin and, a laminin A variant called Merosin A, which is about 40% homologous with the Ae chain.
Variants laminins include Merosin laminin, mouse heart laminin, and S-laminin. Merosin contains a B1e chain, a B2e chain, and a third chain, called Merosin A. This chain is distinct from the EHS-laminin A chain, and shares only about 30% homology by sequence analysis. (Ehrig et al., Proc. Natl. Acad. Sci. 87:3264-3268 (1990)). Mouse heart laminin is a laminin with a substituted A chain. (Saladin et al., J. Biol. Chem. 264:18726-18732 (1989)). S-laminin contains the EHS-laminin B2e and Ae chains, and a variant B1 chain, B1s, which shows some sequence homology to the EHS-B1e chain (Hunter et al., Nature 338:222-234). Recently, another variant of laminin comprising a complex of the S-laminin B1s chain, the EHS B2e chain, and the merosin A chain was also isolated from certain tissues, including the myotendonous junction (Engvall et al., Cell Regulation. 1:731-740 (1990)). Three other variants, rat RN22 laminin (Davis et al., J. Neuroscience 5:2662 (1985); Edgar et al., J. Cell Biol. 106:1299 (1988)), 3T3 adipocyte laminin (Aratani et al, J. Biol. Chem. 263:16163 (1988)), and rat astrocyte laminin (Liesi et al., Exp. Neurol. 105:86-92 (1989)), have also been reported.